The measurement of total calcium in blood has been used in the clinical practice for many years for routine diagnosis by physicians.
During the past several years, the measurement of ionized calcium (Ca.sup.++, free calcium ions) has been recommended to provide an indicator which is more effective than total calcium in cases such as hyperparathyroidism, pancreatitis, renal diseases, and hypocalcemia resulting from repeated blood transfusion, malignancy, and other causes. Furthermore, it is also thought that the simultaneous measurement of both total and ionized calcium is beneficial in the clarification of certain diagnosis. For example, in some clinical cases of multiple myeloma in which hypercalcemia becomes a severe complication, the total calcium in patients is highly elevated while their ionized calcium is normal. Therefore both total and ionized calcium measurements are needed to provide information for a proper diagnosis.
Various instrumentation systems have been developed for the determination of both total and ionized calcium. In the recent past, these instruments have utilized ion-selective-electrodes (ISE) for calcium and other electrolyte measurements. In addition, there has been the development of blood gas analyzers to which electrolyte analysis capabilities have been included through the integration of ion selective electrodes with electrodes for measurement of pH, pCO.sub.2 and pO.sub.2. Furthermore, the capability for measuring a variety of other parameters (e.g., total hemoglobin, hematocrit, glucose) has also been included in some of these instruments.
It is common practice to employ a control solution for verifying the accuracy and reliability of diagnostic instrumentation systems. When analyzed by the instrumentation for which they are intended, these control solutions should closely mimic actual patient samples for both normal and abnormal conditions.
For instrumentation systems which measure both blood gas and ionized calcium along with other electrolytes (such as Na, K, Li and Cl), a single control solution is needed. To date, this has been accomplished in aqueous solutions by incorporating soluble salts of the desired electrolytes into the buffered aqueous solution which has been tonometered with carbon dioxide and oxygen to provide the pH, pCO.sub.2 and pO.sub.2 control values needed for quality control of blood gas analyzers.
Using soluble calcium salts in such a solution, it is very difficult to stabilize the calcium ions in the solution in a satisfactory manner. This is because of the tendency of free ionic calcium to combine with anions and precipitate out of solution. Also, soluble calcium salts are completely ionized and only a small portion of the ionized calcium ion is bound if anions such as phosphate, sulfate, bicarbonate, organic acid buffers or combinations of these are present in the same solution. This results in a low binding of calcium, typically less than 15% of the total calcium, with more than 85% of the calcium in ionized form.
A solution for the quality control of calcium of this nature can provide control values for ionized calcium, but does not provide an effective range of total calcium values to simulate the dynamic range of patient samples.